We have preliminary results indicating that elevation of plasma fatty acids in exercise rats partially inhibits glucose uptake and glycogen breakdown in the red types of skeletal muscle. We propose to follow up this finding with studies of the regulatory mechanisms by which elevation of FFA levels inhibits carbohydrate utilization in red skeletal muscle during exercise. These studies are being conducted on (a) intact rats running on a treadmill, and (b) perfused skeletal muscle in which substrate concentration can be accurately controlled. We also plan to obtain information regarding why glycogen appears to be an indispensable substrate for skeletal muscle during prolonged heavy exercise. This problem is being investigated in perfused, working muscle.